Acid stable polypeptides have been isolated from tumor cells grown both in culture and in the animal. (Roberts et. al. Proc. Natl. Acad. Sci, in press). These proteins are able to produce a reversible morphological transformation of normal rat kidney fibroblast cells that allows them to grow in a soft agar medium where normal cell growth is prevented. It is the purpose of this project to ascertain whether such transforming growth factors are present in human tumor cells and the role these factors may play in the process of carcinogenesis. Initial investigation will concentrate on determination of the amount of such transforming growth factors in several different human cell lines and their properties with a special emphasis on purification and physical characterization. Once these proteins have been characterized, analogs will be synthesized and tested for their ability to inhibit the transforming activity of the natural peptide and therefore, possibly, inhibit the carcinogenic process. Finally, the mechanism whereby these factors interact with the cell to cause the phenotypic cell transformation will be investigated in the hope of offering a greater understanding of carcinogenesis itself.